WO2021246487A1 - Film for wrapping tablets - Google Patents

Film for wrapping tablets Download PDF

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Publication number
WO2021246487A1
WO2021246487A1 PCT/JP2021/021193 JP2021021193W WO2021246487A1 WO 2021246487 A1 WO2021246487 A1 WO 2021246487A1 JP 2021021193 W JP2021021193 W JP 2021021193W WO 2021246487 A1 WO2021246487 A1 WO 2021246487A1
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WO
WIPO (PCT)
Prior art keywords
film
cup portion
film according
cup
additive
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PCT/JP2021/021193
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French (fr)
Japanese (ja)
Inventor
剛 長池
崇弘 松本
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第一三共株式会社
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Priority to JP2022528891A priority Critical patent/JPWO2021246487A1/ja
Publication of WO2021246487A1 publication Critical patent/WO2021246487A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
    • A61J3/06—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of pills, lozenges or dragees
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
    • A61J3/07—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of capsules or similar small containers for oral use
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
    • B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
    • B65D77/00—Packages formed by enclosing articles or materials in preformed containers, e.g. boxes, cartons, sacks or bags
    • B65D77/10—Container closures formed after filling
    • B65D77/20—Container closures formed after filling by applying separate lids or covers, i.e. flexible membrane or foil-like covers
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J5/00—Manufacture of articles or shaped materials containing macromolecular substances
    • C08J5/18—Manufacture of films or sheets
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K5/00—Use of organic ingredients
    • C08K5/04—Oxygen-containing compounds
    • C08K5/05—Alcohols; Metal alcoholates
    • C08K5/053—Polyhydroxylic alcohols
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K5/00—Use of organic ingredients
    • C08K5/04—Oxygen-containing compounds
    • C08K5/10—Esters; Ether-esters
    • C08K5/101—Esters; Ether-esters of monocarboxylic acids
    • C08K5/103—Esters; Ether-esters of monocarboxylic acids with polyalcohols
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K5/00—Use of organic ingredients
    • C08K5/04—Oxygen-containing compounds
    • C08K5/10—Esters; Ether-esters
    • C08K5/11—Esters; Ether-esters of acyclic polycarboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L1/00—Compositions of cellulose, modified cellulose or cellulose derivatives
    • C08L1/02—Cellulose; Modified cellulose
    • C08L1/04—Oxycellulose; Hydrocellulose, e.g. microcrystalline cellulose
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L71/00—Compositions of polyethers obtained by reactions forming an ether link in the main chain; Compositions of derivatives of such polymers
    • C08L71/02—Polyalkylene oxides

Definitions

  • the present disclosure relates to a film for wrapping a tablet, a method for producing a tablet, a tablet, and a method for improving the shape retention and / or chemical stability of the tablet.
  • One of the methods used in the production of orally-administered pharmaceutical preparations is to add additives such as excipients, binders or disintegrants to the active ingredient, compress-mold the homogenized powder, and then use light.
  • Some tablets are coated with a film in consideration of deterioration of quality or use by patients.
  • the solvent used for film coating may affect the stability of the active ingredient.
  • Examples of the pharmaceutical product other than tablets include capsules.
  • Capsules are produced, for example, by filling preformed capsules with powder of the active ingredient and sealing them.
  • capsules have only standardized shapes and standardized sizes in principle, it is difficult to give capsules a characteristic appearance like tablets.
  • the amount of powder that can be filled in the capsule decreases, and the capsule becomes large.
  • some capsules are easy to open, in which case the contents of the capsule can be replaced.
  • the mechanism of the capsule filling machine is used in the powder filling of these formulations, it is difficult to control the filling powder amount with high accuracy.
  • a molded product containing a medicinal ingredient of an orally administered preparation may be wrapped with a thermoplastic sheet or film.
  • a cup portion having an opening is formed by pressing a mold against a thermoplastic sheet or film, and a molded product containing a medicinal ingredient is inserted into the cup portion, and then the cup portion is formed.
  • a method of forming a lid portion for sealing the opening of the above has been studied (Patent Documents 1 to 3).
  • a film containing hypromellose or hydroxypropyl cellulose By using a film containing hypromellose or hydroxypropyl cellulose, it is possible to wrap the molded product containing the medicinal ingredient while ensuring the elution of the medicinal ingredient.
  • a film containing hypromellose or hydroxypropyl cellulose requires a relatively high molding temperature to form a cup portion for accommodating a molded product containing a medicinal ingredient.
  • one aspect of the present disclosure relates to a film containing at least one polymer of hypromellose or hydroxypropyl cellulose and capable of forming a cup portion for accommodating a molded product containing a medicinal ingredient at a lower molding temperature.
  • One aspect of the present disclosure comprises at least one polymer of hypromellose or hydroxypropyl cellulose and at least one additive selected from the group consisting of triethyl citrate, triacetin, propylene glycol, ethylene glycol, polyethylene glycol and sugar alcohols.
  • at least one additive selected from the group consisting of triethyl citrate, triacetin, propylene glycol, ethylene glycol, polyethylene glycol and sugar alcohols.
  • Another aspect of the present disclosure is to form a cup portion forming an opening by pressing the heated film according to the one aspect of the present disclosure against a mold, and to form a medicinal ingredient in the cup portion.
  • To produce a tablet comprising inserting a molded body containing the above, forming a lid portion closing the opening with a film for a lid portion, thereby wrapping the molded body with the lid portion and the cup portion. Provide a way to do it.
  • Yet another aspect of the present disclosure is to provide a tablet comprising a molded body containing a medicinal ingredient, a cup portion accommodating the molded body and forming an opening, and a lid portion closing the opening.
  • the cup portion is the film according to one aspect of the present disclosure.
  • Yet another aspect of the present disclosure comprises wrapping a molded product containing a medicinal ingredient with one or more films comprising the film according to one aspect of the present disclosure, including tablet shape retention and / or chemistry. Provides a way to improve physical stability.
  • FIGS. 1 and 2 are schematic views showing an example of a method for producing a tablet.
  • the methods shown in FIGS. 1 and 2 are to prepare the film 1 for the cup portion as shown in (a) and to heat the film 1 for the cup portion as shown in (b) and (c). Is pressed against the mold 30 to form a cup portion 10 forming an opening, and as shown in (d), the remaining portion 1C of the cup portion film 1 other than the cup portion 10 is formed. Removing the portion so as to remain, inserting the granular molded body 5 containing the medicinal ingredient into the cup portion 10 as shown in (e), and the film 1 for the cup portion as shown in (f).
  • the remaining portion 1C other than the cup portion 10 is removed, and the lid portion 20 that closes the opening of the cup portion 10 is formed by the lid portion film 2 as shown in (g), whereby the lid portion 20 and the cup are formed.
  • the wrapping of the molded body 5 by the portion 10 and the removal of the remaining portion 2C of the lid portion film 2 other than the lid portion 20 as shown in (h) are included in this order.
  • “wrapping the molded product” means that the molded product is enclosed in one or more films.
  • the film 1 for a cup portion is a single-layer film containing at least one polymer of hypromellose or hydroxypropyl cellulose and an additive.
  • the additive is at least one selected from the group consisting of triethyl citrate, triacetin, propylene glycol, ethylene glycol, polyethylene glycol and sugar alcohol.
  • the molecular weight of polyethylene glycol may be 10,000 or less from the viewpoint of moldability of the film 1 for the cup portion.
  • the sugar alcohol may be, for example, sorbitol, erythritol, or xylitol.
  • the additive may be at least one selected from the group consisting of triethyl citrate, triacetin, propylene glycol, ethylene glycol, and polyethylene glycol, or the group consisting of triethyl citrate and triacetin.
  • the content of the additive may be, for example, 5 to 30% by mass, 5 to 20% by mass, or 5 to 15% by mass based on the total amount of the polymer and the additive.
  • the content of the additive is 30% by mass or less, it is easy to obtain a film 1 for a cup portion which has good moldability, is less likely to cause wrinkles, and is excellent in handleability.
  • the tensile elastic modulus of the film 1 for the cup portion may be 800 MPa or more or 900 MPa or more.
  • the upper limit of the tensile elastic modulus of the film 1 for the cup portion is not particularly limited, but is, for example, about 2300 MPa. The method for measuring the tensile elastic modulus will be described in Examples described later.
  • the film 1 for the cup portion may further contain a dye.
  • the film 1 for a cup portion containing a dye can give a colored tablet.
  • the dye may be, for example, an inorganic pigment such as titanium oxide, iron sesquioxide, or yellow iron sesquioxide, a synthetic tar dye, or a combination thereof.
  • the content of the dye (particularly the inorganic pigment) may be, for example, 30% by mass or less based on the total amount of the polymer and the additive.
  • the film 1 for the cup portion may further contain other components in addition to the polymers, additives and dyes exemplified above.
  • other ingredients include flavoring agents.
  • the content of other components may be 10% by mass or less, 5% by mass or less, 3% by mass or less, or 1% by mass or less based on the mass of the film 1 for the cup portion.
  • the thickness of the film 1 for the cup portion may be, for example, 40 to 80 ⁇ m or 20 to 100 ⁇ m.
  • the film for the cup portion is not limited to the film consisting of only the single-layer film for the cup portion 1 as in the example shown in FIG.
  • the film for the cup portion may have a base film containing the above-mentioned polymer and additives, and an adhesive layer provided on the base film.
  • the adhesive layer may be, for example, a layer containing copolyvidone, methacrylic acid copolymer LD, ethyl acrylate / methyl methacrylate copolymer, polyvinylpyrrolidone, or aminoalkyl methacrylate copolymer E.
  • the film 1 for a cup portion is obtained by applying a coating liquid containing, for example, a polymer, an additive and other components added as necessary, and water to a substrate having a smooth flat surface portion such as a glass plate, and coating the film 1. It can be obtained by methods including drying the membrane.
  • the heated cup film 1 is pressed against the mold 30 to create a negative pressure in the gap between the cup film 1 and the mold 30, whereby the bottom portion 1A and the wall portion 1B extending from the peripheral edge of the bottom portion 1A are formed. , A cup portion 10 having an opening formed by the end portion of the wall portion 1B is formed.
  • the mold 30 may be moved toward the fixed cup film 1, or the cup film 1 may be moved toward the fixed mold 30. You may.
  • the remaining portion 1C of the cup portion film 1 other than the cup portion 10 is usually left around the cup portion 10 to some extent.
  • the shape and size of the cup portion 10 are adjusted so that the molded body 5 can be accommodated.
  • the bottom portion 1A may be curved as shown or may be flat.
  • the maximum value of the depth of the cup portion 10 depth from the remaining portion 1C may be, for example, 8 mm or less.
  • the maximum width of the cup portion 10 (the maximum value of the distance between the inner surfaces of the cup portion 10 when viewed from the depth direction of the cup portion 10) may be, for example, 16 mm or less.
  • the temperature (molding temperature) of the cup portion film 1 pressed against the mold 30 is a temperature adjusted so that the cup portion 10 having a desired shape is appropriately formed, and is, for example, the cup portion film 1 to be molded.
  • the temperature is 100 to 180 ° C. or 120 to 160 ° C.
  • the time for pressing the mold 30 against the cup film 1 may be a range that does not affect the normal formation of the film.
  • the film 1 for the cup portion may be cut along the opening of the cup portion 10 by irradiation with a laser beam.
  • the molded body 5 containing the medicinal ingredient is inserted into the cup portion 10.
  • the molded body 5 can be formed, for example, by compression molding of a powder containing a medicinal ingredient and other components added as necessary.
  • the molded body may have a score line. Examples of non-medicinal ingredients include excipients, binders, disintegrants, lubricants, stabilizers, and preservatives.
  • the maximum width of the molded body 5 is usually about the same as the maximum width of the cup portion 10.
  • the remaining portion 1C is removed by a method such as irradiation with a laser beam.
  • the heated lid film 2 is pressed against the exposed surface of the molded body 5 of the cup portion 10 into which the molded body 5 is inserted.
  • the lid portion is formed and the film 2 for the lid portion is joined to the cup portion 10.
  • the entire surface of the molded body 5 is covered with the lid portion 20 composed of the ceiling portion 2A covering a part of the surface of the molded body 5 and the wall portion 2B extending from the peripheral edge thereof, and the cup portion 10. ..
  • the molded body 5 is wrapped by the lid portion 20 and the cup portion 10.
  • the temperature (molding temperature) of the lid film 2 pressed against the cup 10 into which the molded body 5 is inserted is a temperature adjusted so that the lid 20 having a desired shape is appropriately formed.
  • the molding temperature may be 100 to 180 ° C. or 120 to 160 ° C.
  • the film 2 for the lid portion is a thermoplastic film, and may be, for example, the same film as the film 1 for the cup portion. Since the inner surface of the wall portion 2B of the lid portion 20 and the outer surface of the wall portion 1B of the cup portion 10 are adhered to each other, the lid portion 20 (film for the lid portion 2) has the same base as the film 1 for the cup portion. It may have a material film and an adhesive layer provided on the inner surface of the base film.
  • the remaining portion 2C of the lid portion film 2 other than the lid portion 20 is removed by a method such as irradiation with a laser beam.
  • a treatment such as heat shrinkage is performed as necessary, so that the molded body 5, the cup portion 10 in which the molded body 5 is housed, and the lid joined to the cup portion 10 so that the molded body 5 is enclosed are sealed.
  • a tablet 50 composed of a portion 20 is obtained.
  • the film according to the present embodiment can also be used to improve the shape retention and / or the chemical stability of an existing tablet having a molded product containing a medicinal ingredient.
  • the coating liquid containing each raw material was prepared according to the formulations shown in Table 1, Table 2 or Table 3.
  • the formulations listed in each table are shown as a percentage (% by weight) based on the total amount of polymer (hypromellose or hydroxypropyl cellulose) and additives.
  • the additive was dissolved in a mixed solvent of purified water / ethanol (volume ratio: 50/50).
  • Hypromellose or hydroxypropyl cellulose was dissolved in the obtained aqueous solution to obtain a coating liquid for film formation.
  • the glass plate was coated with a certain thickness using an electric film applicator.
  • the coating film was naturally dried all day and night to form a film having a film thickness of 60 ⁇ m. Films having a film thickness of 40 ⁇ m or 80 ⁇ m were also prepared using the coating solutions of Formulations 2 and 3.
  • FIG. 3 is a photograph showing an example of a cup portion formed by a molding test.
  • "1" is an example of "moldable”
  • "2" and “3" are examples of “non-moldable”.
  • the lowest temperature was recorded as the "moldable set temperature”. For example, when the set temperature of the heater for heating the film is about 400 ° C, the temperature of the heater outlet is 305 to 310 ° C, the temperature near the upper surface of the film at that time is 230 ° C, and the temperature of the lower surface of the film at that time is the maximum. It was 120 ° C.

Abstract

Provided is a film including: a polymer of at least one of hypromellose and hydroxypropyl cellulose; and at least one additive selected from the group consisting of triethyl citrate, triacetin, propylene glycol, ethylene glycol, polyethylene glycol, and sugar alcohols. The film is for use in wrapping molded bodies containing a medicinal ingredient.

Description

錠剤をラッピングするためのフィルムFilm for wrapping tablets
　本開示は、錠剤をラッピングするためのフィルム、錠剤を製造する方法、錠剤、及び、錠剤の形状保持性及び／又は化学的安定性を向上する方法に関する。 The present disclosure relates to a film for wrapping a tablet, a method for producing a tablet, a tablet, and a method for improving the shape retention and / or chemical stability of the tablet.
　経口投与する医薬の製剤を製造するにあたり、用いられる方法のひとつとして、有効成分に賦形剤、結合剤又は崩壊剤等の添加剤を加えて均質化した粉体を圧縮成形した後、光による品質の劣化あるいは患者の使用を考慮してフィルムコーティングを施して錠剤化するものがある。しかしながら、有効成分の種類によっては、市場において流通し、又は処方、投薬するために必要十分な硬度を有した錠剤を打錠することが困難であることがある。フィルムコーティングの際の物理的な衝撃によって成形体の一部が破損するために錠剤の品質が損なわれることもある。また、フィルムコーティングの際に使用する溶媒により、有効成分の安定性に影響を及ぼすこともある。 One of the methods used in the production of orally-administered pharmaceutical preparations is to add additives such as excipients, binders or disintegrants to the active ingredient, compress-mold the homogenized powder, and then use light. Some tablets are coated with a film in consideration of deterioration of quality or use by patients. However, depending on the type of active ingredient, it may be difficult to tablet tablets having sufficient hardness to be distributed on the market or to be formulated or administered. Physical impact during film coating can also impair the quality of the tablet by damaging part of the molding. In addition, the solvent used for film coating may affect the stability of the active ingredient.
　錠剤以外の態様の製剤としては、カプセル剤が挙げられる。カプセル剤は、例えば、予め成形したカプセルに有効成分の粉体を充填して封止することにより製造される。だが、カプセル剤には、原則として定型の画一的な形状及び規格化されたサイズのものしか存在しないため、錠剤のように特徴のある外観をカプセル剤に与えることは困難である。また、粉末が充填されたカプセル内には空隙があるため、カプセル内に充填できる粉体量が減り、カプセルが大型化してしまう。さらに、カプセルによっては開封が容易なものがあり、その場合、カプセルの内容物を入れ替えることができる。一方で、熱可塑性フィルムで成形したカップに充填した粉体を、杵で圧縮してから封止することで製造される態様の製剤がある。しかし、これらの製剤の粉末充填においてはカプセル充填機の機構を用いているため、充填粉末量を高精度に制御することが難しい。 Examples of the pharmaceutical product other than tablets include capsules. Capsules are produced, for example, by filling preformed capsules with powder of the active ingredient and sealing them. However, since capsules have only standardized shapes and standardized sizes in principle, it is difficult to give capsules a characteristic appearance like tablets. Further, since there are voids in the capsule filled with the powder, the amount of powder that can be filled in the capsule decreases, and the capsule becomes large. Further, some capsules are easy to open, in which case the contents of the capsule can be replaced. On the other hand, there is an embodiment of a pharmaceutical product produced by compressing a powder filled in a cup formed of a thermoplastic film with a pestle and then sealing the powder. However, since the mechanism of the capsule filling machine is used in the powder filling of these formulations, it is difficult to control the filling powder amount with high accuracy.
　このような課題を解決する手段として、経口投与される製剤の薬効成分を含む成形体が熱可塑性のシート又はフィルムによってラッピングされることがある。そのような態様の製剤を製造するために、熱可塑性のシート又はフィルムに型を押し当てることにより開口を有するカップ部を形成し、カップ部に薬効成分を含む成形体を挿入し、次いでカップ部の開口を封止する蓋部を形成する方法が検討されている（特許文献１～３）。 As a means for solving such a problem, a molded product containing a medicinal ingredient of an orally administered preparation may be wrapped with a thermoplastic sheet or film. In order to produce a formulation of such an embodiment, a cup portion having an opening is formed by pressing a mold against a thermoplastic sheet or film, and a molded product containing a medicinal ingredient is inserted into the cup portion, and then the cup portion is formed. A method of forming a lid portion for sealing the opening of the above has been studied (Patent Documents 1 to 3).
国際公開第２０１８／０７４２５９号International Publication No. 2018/074259 国際公開第２０１８／０７４２６０号International Publication No. 2018/074260 国際公開第２０１８／０７４２６１号International Publication No. 2018/074261
　ヒプロメロース又はヒドロキシプロピルセルロースを含むフィルムを用いることにより、薬効成分の溶出性を確保しながら、薬効成分を含む成形体をラッピングすることができる。しかし、ヒプロメロース又はヒドロキシプロピルセルロースを含むフィルムは、薬効成分を含む成形体を収容するためのカップ部を形成するために、比較的高い成形温度を必要とする。 By using a film containing hypromellose or hydroxypropyl cellulose, it is possible to wrap the molded product containing the medicinal ingredient while ensuring the elution of the medicinal ingredient. However, a film containing hypromellose or hydroxypropyl cellulose requires a relatively high molding temperature to form a cup portion for accommodating a molded product containing a medicinal ingredient.
　そこで本開示の一側面は、ヒプロメロース又はヒドロキシプロピルセルロースのうち少なくとも一方のポリマーを含み、薬効成分を含む成形体を収容するためのカップ部をより低い成形温度で形成できるフィルムに関する。 Therefore, one aspect of the present disclosure relates to a film containing at least one polymer of hypromellose or hydroxypropyl cellulose and capable of forming a cup portion for accommodating a molded product containing a medicinal ingredient at a lower molding temperature.
　本開示の一側面は、ヒプロメロース又はヒドロキシプロピルセルロースのうち少なくとも一方のポリマーと、クエン酸トリエチル、トリアセチン、プロピレングリコール、エチレングリコール、ポリエチレングリコール及び糖アルコールからなる群より選ばれる少なくとも１種の添加剤と、を含み、薬効成分を含む成形体をラッピングするために用いられるフィルムを提供する。 One aspect of the present disclosure comprises at least one polymer of hypromellose or hydroxypropyl cellulose and at least one additive selected from the group consisting of triethyl citrate, triacetin, propylene glycol, ethylene glycol, polyethylene glycol and sugar alcohols. To provide a film used for wrapping a molded product containing, and containing a medicinal ingredient.
　本開示の別の一側面は、加熱された本開示の一側面に係る上記フィルムを型に押し当てることにより、開口を形成しているカップ部を形成することと、前記カップ部内に、薬効成分を含む成形体を挿入することと、前記開口を塞ぐ蓋部を蓋部用フィルムによって形成し、それにより前記蓋部及び前記カップ部によって前記成形体をラッピングすることと、を含む、錠剤を製造する方法を提供する。 Another aspect of the present disclosure is to form a cup portion forming an opening by pressing the heated film according to the one aspect of the present disclosure against a mold, and to form a medicinal ingredient in the cup portion. To produce a tablet comprising inserting a molded body containing the above, forming a lid portion closing the opening with a film for a lid portion, thereby wrapping the molded body with the lid portion and the cup portion. Provide a way to do it.
　本開示の更に別の一側面は、薬効成分を含む成形体と、前記成形体を収容し、開口を形成しているカップ部と、前記開口を塞ぐ蓋部と、を備える錠剤を提供する。前記カップ部は、本開示の一側面に係る上記フィルムである。 Yet another aspect of the present disclosure is to provide a tablet comprising a molded body containing a medicinal ingredient, a cup portion accommodating the molded body and forming an opening, and a lid portion closing the opening. The cup portion is the film according to one aspect of the present disclosure.
　本開示の更に別の一側面は、薬効成分を含む成形体を、本開示の一側面に係る上記フィルムを含む１枚以上のフィルムによってラッピングすることを含む、錠剤の形状保持性及び／又は化学的安定性を向上する方法を提供する。 Yet another aspect of the present disclosure comprises wrapping a molded product containing a medicinal ingredient with one or more films comprising the film according to one aspect of the present disclosure, including tablet shape retention and / or chemistry. Provides a way to improve physical stability.
　本開示の一側面によれば、ヒプロメロース又はヒドロキシプロピルセルロースのうち少なくとも一方のポリマーを含み、薬効成分を含む成形体を収容するためのカップ部をより低い成形温度で形成できるフィルムが提供される。 According to one aspect of the present disclosure, there is provided a film containing at least one polymer of hypromellose or hydroxypropyl cellulose and capable of forming a cup portion for accommodating a molded product containing a medicinal ingredient at a lower molding temperature.
錠剤を製造する方法の一例を示す模式図である。It is a schematic diagram which shows an example of the method of manufacturing a tablet. 錠剤を製造する方法の一例を示す模式図である。It is a schematic diagram which shows an example of the method of manufacturing a tablet. 成形試験により形成されたカップ部の例を示す写真である。It is a photograph which shows the example of the cup part formed by the molding test.
　以下、本発明のいくつかの実施形態について詳細に説明する。ただし、本発明は以下の実施形態に限定されるものではない。 Hereinafter, some embodiments of the present invention will be described in detail. However, the present invention is not limited to the following embodiments.
　図１及び図２は、錠剤を製造する方法の一例を示す模式図である。図１及び図２に示される方法は、（ａ）に示されるようにカップ部用フィルム１を準備することと、（ｂ）及び（ｃ）に示されるように加熱されたカップ部用フィルム１を型３０に押し当てることにより、開口を形成しているカップ部１０を形成することと、（ｄ）に示されるようにカップ部用フィルム１のうちカップ部１０以外の残部１Ｃを、その一部が残るように除去することと、（ｅ）に示されるようにカップ部１０に薬効成分を含む粒状の成形体５を挿入することと、（ｆ）に示されるようにカップ部用フィルム１のうちカップ部１０以外の残部１Ｃを除去することと、（ｇ）に示されるようにカップ部１０の開口を塞ぐ蓋部２０を蓋部用フィルム２によって形成し、それにより蓋部２０及びカップ部１０によって成形体５をラッピングすることと、（ｈ）に示されるように蓋部用フィルム２のうち蓋部２０以外の残部２Ｃを除去することとをこの順に含む。ここで、「成形体をラッピングする」とは、１枚以上のフィルム内に成形体が封入されることを意味する。 1 and 2 are schematic views showing an example of a method for producing a tablet. The methods shown in FIGS. 1 and 2 are to prepare the film 1 for the cup portion as shown in (a) and to heat the film 1 for the cup portion as shown in (b) and (c). Is pressed against the mold 30 to form a cup portion 10 forming an opening, and as shown in (d), the remaining portion 1C of the cup portion film 1 other than the cup portion 10 is formed. Removing the portion so as to remain, inserting the granular molded body 5 containing the medicinal ingredient into the cup portion 10 as shown in (e), and the film 1 for the cup portion as shown in (f). Of these, the remaining portion 1C other than the cup portion 10 is removed, and the lid portion 20 that closes the opening of the cup portion 10 is formed by the lid portion film 2 as shown in (g), whereby the lid portion 20 and the cup are formed. The wrapping of the molded body 5 by the portion 10 and the removal of the remaining portion 2C of the lid portion film 2 other than the lid portion 20 as shown in (h) are included in this order. Here, "wrapping the molded product" means that the molded product is enclosed in one or more films.
　一実施形態に係るカップ部用フィルム１は、ヒプロメロース又はヒドロキシプロピルセルロースのうち少なくとも一方のポリマーと、添加剤とを含む単層のフィルムである。 The film 1 for a cup portion according to one embodiment is a single-layer film containing at least one polymer of hypromellose or hydroxypropyl cellulose and an additive.
　添加剤は、クエン酸トリエチル、トリアセチン、プロピレングリコール、エチレングリコール、ポリエチレングリコール及び糖アルコールからなる群より選ばれる少なくとも１種である。ポリエチレングリコールの分子量は、カップ部用フィルム１の成形性等の観点から１００００以下であってもよい。糖アルコールは、例えばソルビトール、エリスリトール、又はキシリトールであってもよい。 The additive is at least one selected from the group consisting of triethyl citrate, triacetin, propylene glycol, ethylene glycol, polyethylene glycol and sugar alcohol. The molecular weight of polyethylene glycol may be 10,000 or less from the viewpoint of moldability of the film 1 for the cup portion. The sugar alcohol may be, for example, sorbitol, erythritol, or xylitol.
　添加剤は、クエン酸トリエチル、トリアセチン、プロピレングリコール、エチレングリコール、及びポリエチレングリコールからなる群、又は、クエン酸トリエチル及びトリアセチンからなる群より選ばれる少なくとも１種であってもよい。 The additive may be at least one selected from the group consisting of triethyl citrate, triacetin, propylene glycol, ethylene glycol, and polyethylene glycol, or the group consisting of triethyl citrate and triacetin.
　添加剤の含有量は、ポリマー及び添加剤の合計量を基準として例えば５～３０質量％、５～２０質量％、又は５～１５質量％であってもよい。添加剤の含有量が３０質量％以下であると、良好な成形性を有するとともに、しわを生じ難く、取扱い性に優れたカップ部用フィルム１が得られ易い。 The content of the additive may be, for example, 5 to 30% by mass, 5 to 20% by mass, or 5 to 15% by mass based on the total amount of the polymer and the additive. When the content of the additive is 30% by mass or less, it is easy to obtain a film 1 for a cup portion which has good moldability, is less likely to cause wrinkles, and is excellent in handleability.
　取扱い性等の観点から、カップ部用フィルム１の引張弾性率が、８００ＭＰａ以上、又は９００ＭＰａ以上であってもよい。カップ部用フィルム１の引張弾性率の上限は、特に制限されないが、例えば２３００ＭＰａ程度である。引張弾性率の測定方法は後述の実施例において説明される。 From the viewpoint of handleability and the like, the tensile elastic modulus of the film 1 for the cup portion may be 800 MPa or more or 900 MPa or more. The upper limit of the tensile elastic modulus of the film 1 for the cup portion is not particularly limited, but is, for example, about 2300 MPa. The method for measuring the tensile elastic modulus will be described in Examples described later.
　カップ部用フィルム１が色素を更に含んでもよい。色素を含むカップ部用フィルム１は、着色した錠剤を与えることができる。色素は、例えば、酸化チタン、三二酸化鉄、黄色三二酸化鉄等の無機顔料、合成タール色素、又はこれらの組み合わせであってもよい。色素（特に無機顔料）の含有量は、ポリマー及び添加剤の合計量を基準として、例えば３０質量％以下であってもよい。 The film 1 for the cup portion may further contain a dye. The film 1 for a cup portion containing a dye can give a colored tablet. The dye may be, for example, an inorganic pigment such as titanium oxide, iron sesquioxide, or yellow iron sesquioxide, a synthetic tar dye, or a combination thereof. The content of the dye (particularly the inorganic pigment) may be, for example, 30% by mass or less based on the total amount of the polymer and the additive.
　カップ部用フィルム１は、以上例示されたポリマー、添加剤及び色素の他に、その他の成分を更に含んでもよい。その他の成分の例としては、矯味剤が挙げられる。その他の成分の含有量は、カップ部用フィルム１の質量を基準として１０質量％以下、５質量％以下、３質量％以下、又は１質量％以下であってもよい。 The film 1 for the cup portion may further contain other components in addition to the polymers, additives and dyes exemplified above. Examples of other ingredients include flavoring agents. The content of other components may be 10% by mass or less, 5% by mass or less, 3% by mass or less, or 1% by mass or less based on the mass of the film 1 for the cup portion.
　カップ部用フィルム１の厚さは、例えば４０～８０μｍ、又は２０～１００μｍであってもよい。 The thickness of the film 1 for the cup portion may be, for example, 40 to 80 μm or 20 to 100 μm.
　カップ部用フィルムは、図１に示される例のように単層のカップ部用フィルム１のみからなるフィルムに限られない。例えば、カップ部用フィルムが、上述のポリマー及び添加剤を含む基材フィルムと、その基材フィルム上に設けられた接着層とを有していてもよい。接着層が設けられると、カップ部１０と蓋部２０とをより強固に接合することができる。接着層は、例えば、コポリビドン、メタクリル酸コポリマーＬＤ、アクリル酸エチル・メタクリル酸メチルコポリマー、ポリビニルピロリドン、又はアミノアルキルメタクリレートコポリマーＥを含む層であってもよい。 The film for the cup portion is not limited to the film consisting of only the single-layer film for the cup portion 1 as in the example shown in FIG. For example, the film for the cup portion may have a base film containing the above-mentioned polymer and additives, and an adhesive layer provided on the base film. When the adhesive layer is provided, the cup portion 10 and the lid portion 20 can be joined more firmly. The adhesive layer may be, for example, a layer containing copolyvidone, methacrylic acid copolymer LD, ethyl acrylate / methyl methacrylate copolymer, polyvinylpyrrolidone, or aminoalkyl methacrylate copolymer E.
　カップ部用フィルム１は、例えば、ポリマー、添加剤及び必要により加えられるその他の成分と、水とを含む塗工液をガラス板等の滑らかな平面部を有する基材に塗布することと、塗膜を乾燥することとを含む方法によって得ることができる。 The film 1 for a cup portion is obtained by applying a coating liquid containing, for example, a polymer, an additive and other components added as necessary, and water to a substrate having a smooth flat surface portion such as a glass plate, and coating the film 1. It can be obtained by methods including drying the membrane.
　加熱されたカップ部用フィルム１を型３０に押し当て、カップ部用フィルム１と型３０との間の空隙を陰圧にすることにより、底部１Ａ及び底部１Ａの周縁から延びる壁部１Ｂからなり、壁部１Ｂの端部によって形成された開口を有するカップ部１０が形成される。カップ部用フィルム１に型３０を押し当てるために、固定されたカップ部用フィルム１に向けて型３０を移動させてもよく、固定された型３０に向けてカップ部用フィルム１を移動させてもよい。型３０がカップ部用フィルム１から離された時点では、通常、カップ部用フィルム１のうちカップ部１０以外の残部１Ｃが、カップ部１０の周囲にある程度残される。カップ部１０の形状及びサイズは、成形体５が収容できるように調整される。底部１Ａは図示されるように湾曲していてもよいし、平面状であってもよい。カップ部１０の深さ（残部１Ｃからの深さ）の最大値は、例えば８ｍｍ以下であってもよい。カップ部１０の最大幅（カップ部１０の深さ方向から見たときのカップ部１０の内側表面同士の距離の最大値）は、例えば１６ｍｍ以下であってもよい。 The heated cup film 1 is pressed against the mold 30 to create a negative pressure in the gap between the cup film 1 and the mold 30, whereby the bottom portion 1A and the wall portion 1B extending from the peripheral edge of the bottom portion 1A are formed. , A cup portion 10 having an opening formed by the end portion of the wall portion 1B is formed. In order to press the mold 30 against the cup film 1, the mold 30 may be moved toward the fixed cup film 1, or the cup film 1 may be moved toward the fixed mold 30. You may. When the mold 30 is separated from the cup portion film 1, the remaining portion 1C of the cup portion film 1 other than the cup portion 10 is usually left around the cup portion 10 to some extent. The shape and size of the cup portion 10 are adjusted so that the molded body 5 can be accommodated. The bottom portion 1A may be curved as shown or may be flat. The maximum value of the depth of the cup portion 10 (depth from the remaining portion 1C) may be, for example, 8 mm or less. The maximum width of the cup portion 10 (the maximum value of the distance between the inner surfaces of the cup portion 10 when viewed from the depth direction of the cup portion 10) may be, for example, 16 mm or less.
　型３０に押し当てられるカップ部用フィルム１の温度（成形温度）は、所望の形状のカップ部１０が適切に形成されるように調整された温度であり、例えば成形されるカップ部用フィルム１の温度が１００～１８０℃、又は１２０～１６０℃となる温度である。カップ部用フィルム１に型３０を押し当てる時間は、フィルムの正常な形成に影響のない範囲であればよい。 The temperature (molding temperature) of the cup portion film 1 pressed against the mold 30 is a temperature adjusted so that the cup portion 10 having a desired shape is appropriately formed, and is, for example, the cup portion film 1 to be molded. The temperature is 100 to 180 ° C. or 120 to 160 ° C. The time for pressing the mold 30 against the cup film 1 may be a range that does not affect the normal formation of the film.
　カップ部１０が形成された後、カップ部１０周囲の残部１Ｃのうち大部分が除去される。そのために、例えばレーザー光の照射によってカップ部用フィルム１をカップ部１０の開口に沿って切断してもよい。 After the cup portion 10 is formed, most of the remaining portion 1C around the cup portion 10 is removed. Therefore, for example, the film 1 for the cup portion may be cut along the opening of the cup portion 10 by irradiation with a laser beam.
　続いて、カップ部１０に薬効成分を含む成形体５が挿入される。成形体５は、例えば、薬効成分と、その他必要により加えられる成分とを含む粉体の圧縮成形によって形成することができる。成形体には割線があってもよい。薬効成分以外の成分の例は、賦形剤、結合剤、崩壊剤、滑沢剤、安定剤、及び保存剤を含む。成形体５の最大幅は、通常、カップ部１０の最大幅と同程度である。 Subsequently, the molded body 5 containing the medicinal ingredient is inserted into the cup portion 10. The molded body 5 can be formed, for example, by compression molding of a powder containing a medicinal ingredient and other components added as necessary. The molded body may have a score line. Examples of non-medicinal ingredients include excipients, binders, disintegrants, lubricants, stabilizers, and preservatives. The maximum width of the molded body 5 is usually about the same as the maximum width of the cup portion 10.
　成形体５がカップ部１０に挿入された後、残部１Ｃがレーザー光の照射等の方法により除去される。 After the molded body 5 is inserted into the cup portion 10, the remaining portion 1C is removed by a method such as irradiation with a laser beam.
　加熱された蓋部用フィルム２が、成形体５が挿入されたカップ部１０の成形体５が露出している表面に向けて押し当てられる。その結果生じた蓋部用フィルム２とカップ部１０との間の空隙を陰圧にすることにより、蓋部が形成されるとともに、蓋部用フィルム２がカップ部１０と接合される。蓋部用フィルム２のうち、成形体５の表面の一部を覆う天井部２Ａ及びその周縁から延びる壁部２Ｂからなる蓋部２０と、カップ部１０とで成形体５の表面全体が覆われる。言い換えると、蓋部２０及びカップ部１０によって成形体５がラッピングされる。 The heated lid film 2 is pressed against the exposed surface of the molded body 5 of the cup portion 10 into which the molded body 5 is inserted. By creating a negative pressure in the gap between the film 2 for the lid portion and the cup portion 10 that is generated as a result, the lid portion is formed and the film 2 for the lid portion is joined to the cup portion 10. Of the film 2 for the lid portion, the entire surface of the molded body 5 is covered with the lid portion 20 composed of the ceiling portion 2A covering a part of the surface of the molded body 5 and the wall portion 2B extending from the peripheral edge thereof, and the cup portion 10. .. In other words, the molded body 5 is wrapped by the lid portion 20 and the cup portion 10.
　成形体５が挿入されたカップ部１０に押し当てられる蓋部用フィルム２の温度（成形温度）は、所望の形状の蓋部２０が適切に形成されるように調整された温度である。例えば、成形温度が１００～１８０℃、又は１２０～１６０℃であってもよい。 The temperature (molding temperature) of the lid film 2 pressed against the cup 10 into which the molded body 5 is inserted is a temperature adjusted so that the lid 20 having a desired shape is appropriately formed. For example, the molding temperature may be 100 to 180 ° C. or 120 to 160 ° C.
　蓋部用フィルム２は、熱可塑性のフィルムであり、例えばカップ部用フィルム１と同様のフィルムであってもよい。蓋部２０の壁部２Ｂの内側表面と、カップ部１０の壁部１Ｂの外側表面とが接着されるため、蓋部２０（蓋部用フィルム２）が、カップ部用フィルム１と同様の基材フィルムと、その基材フィルムの内側の表面上に設けられた接着層とを有していてもよい。 The film 2 for the lid portion is a thermoplastic film, and may be, for example, the same film as the film 1 for the cup portion. Since the inner surface of the wall portion 2B of the lid portion 20 and the outer surface of the wall portion 1B of the cup portion 10 are adhered to each other, the lid portion 20 (film for the lid portion 2) has the same base as the film 1 for the cup portion. It may have a material film and an adhesive layer provided on the inner surface of the base film.
　蓋部２０が形成された後、蓋部用フィルム２のうち蓋部２０以外の残部２Ｃがレーザー光の照射等の方法により除去される。 After the lid portion 20 is formed, the remaining portion 2C of the lid portion film 2 other than the lid portion 20 is removed by a method such as irradiation with a laser beam.
　その後、加熱収縮等の処理が必要により施されることで、成形体５と、成形体５が収容されたカップ部１０と、成形体５が封入されるようにカップ部１０と接合された蓋部２０とから構成される錠剤５０が得られる。 After that, a treatment such as heat shrinkage is performed as necessary, so that the molded body 5, the cup portion 10 in which the molded body 5 is housed, and the lid joined to the cup portion 10 so that the molded body 5 is enclosed are sealed. A tablet 50 composed of a portion 20 is obtained.
　薬効成分を含む成形体がカップ部用フィルム１及び蓋部用フィルム２から構成される２枚のフィルムによってラッピングされることにより、例えば成形体の形状保存性、抗摩擦強度のような形状保持性、又は成形体の化学的安定性が不足する場合であっても、安定して取り扱うことの可能な錠剤を得ることができる。そのため、本実施形態に係るフィルムを、薬効成分を含む成形体を有する既存の錠剤の形状保持性及び／又は化学的安定性を向上するために用いることもできる。 By wrapping the molded product containing the medicinal properties with two films composed of the film 1 for the cup portion and the film 2 for the lid portion, for example, the shape preservability of the molded body and the shape retention such as the anti-friction strength are maintained. Or, even when the chemical stability of the molded product is insufficient, a tablet that can be handled stably can be obtained. Therefore, the film according to the present embodiment can also be used to improve the shape retention and / or the chemical stability of an existing tablet having a molded product containing a medicinal ingredient.
　以下、実施例を挙げて本発明についてさらに具体的に説明する。ただし、本発明はこれら実施例に限定されるものではない。 Hereinafter, the present invention will be described in more detail with reference to examples. However, the present invention is not limited to these examples.
１．原材料
ヒプロメロース（ヒドロキシプロピルメチルセルロース）
・ＴＣ－５Ｓ（２％水溶液の粘度（２０℃）：１５ｍＰａ・ｓ、信越化学工業）
・ＴＣ－５Ｒ（２％水溶液の粘度（２０℃）：６ｍＰａ・ｓ、信越化学工業）
・ＴＣ－５Ｍ（２％水溶液の粘度（２０℃）：４．５ｍＰａ・ｓ、信越化学工業）
・ＴＣ－５Ｅ（２％水溶液の粘度（２０℃）：３ｍＰａ・ｓ、信越化学工業）
ヒドロキシプロピルセルロース
・ＨＰＣ－Ｍ（日本曹達）
添加剤
・クエン酸トリエチル（森村商事）
・トリアセチン（関東化学）
・プロピレングリコール（関東化学）
・ＰＥＧ４００（三洋化成、ポリエチレングリコール、平均分子量４００）
・コポリビドン（１－ビニル－２－ピロリドンと酢酸ビニルの共重合体（質量比＝３：２）、Ashland）
・ポリビニルピロリドン（ＰＶＰ　Ｋ３０、BASF）
色素（顔料）
・酸化チタン（石原産業） 1. 1. Raw material Hypromellose (hydroxypropylmethylcellulose)
TC-5S (viscosity of 2% aqueous solution (20 ° C.): 15 mPa · s, Shin-Etsu Chemical Co., Ltd.)
TC-5R (viscosity of 2% aqueous solution (20 ° C): 6 mPa · s, Shin-Etsu Chemical Co., Ltd.)
TC-5M (viscosity of 2% aqueous solution (20 ° C): 4.5 mPa · s, Shin-Etsu Chemical Co., Ltd.)
TC-5E (viscosity of 2% aqueous solution (20 ° C): 3 mPa · s, Shin-Etsu Chemical Co., Ltd.)
Hydroxypropyl Cellulose HPC-M (Nippon Soda)
Additive ・ Triethyl citrate (Morimura Brothers)
・ Triacetin (Kanto Chemical Co., Ltd.)
・ Propylene glycol (Kanto Chemical Co., Ltd.)
PEG400 (SANYO CHEMICAL INDUSTRIES, polyethylene glycol, average molecular weight 400)
-Copolyvidone (copolymer of 1-vinyl-2-pyrrolidone and vinyl acetate (mass ratio = 3: 2), Ashland)
-Polyvinylpyrrolidone (PVP K30, BASF)
Pigment (pigment)
・ Titanium oxide (Ishihara Sangyo)
２．フィルムの作製
　以下の手順により、表１、表２又は表３に記載の処方で各原材料を含む塗工液を調整した。各表に記載の処方は、ポリマー（ヒプロメロース又はヒドロキシプロピルセルロース）と添加剤との合計量を基準とする割合（質量％）として示されている。まず添加剤を、精製水／エタノール（体積比：５０／５０）の混合溶媒に溶解させた。得られた水溶液にヒプロメロース又はヒドロキシプロピルセルロースを溶解させて、フィルム形成用の塗工液を得た。塗工液を真空下で脱気してから、電動式フィルムアプリケーターを用いてガラス板に一定の厚みで塗工した。塗膜を一昼夜自然乾燥して、膜厚６０μｍのフィルムを形成した。処方２及び３の塗工液を用いて、膜厚４０μｍ又は８０μｍのフィルムも作製した。 2. 2. Preparation of Film According to the following procedure, the coating liquid containing each raw material was prepared according to the formulations shown in Table 1, Table 2 or Table 3. The formulations listed in each table are shown as a percentage (% by weight) based on the total amount of polymer (hypromellose or hydroxypropyl cellulose) and additives. First, the additive was dissolved in a mixed solvent of purified water / ethanol (volume ratio: 50/50). Hypromellose or hydroxypropyl cellulose was dissolved in the obtained aqueous solution to obtain a coating liquid for film formation. After degassing the coating liquid under vacuum, the glass plate was coated with a certain thickness using an electric film applicator. The coating film was naturally dried all day and night to form a film having a film thickness of 60 μm. Films having a film thickness of 40 μm or 80 μm were also prepared using the coating solutions of Formulations 2 and 3.
３．評価
３－１．引張試験
　各フィルムから、幅１０ｍｍ、長さ５０ｍｍの短冊状の試験片を切り出した。試験片を２５℃、６０ＲＨの環境下で１時間放置してから、ＥＺ－ｔｅｓｔ（島津製作所製）を用いて引張試験を行った。つかみ具間の距離は３０ｍｍ、試験速度は１０ｍｍ／分とした。 3. 3. Evaluation 3-1. Tensile test A strip-shaped test piece having a width of 10 mm and a length of 50 mm was cut out from each film. The test piece was left at 25 ° C. and 60 RH for 1 hour, and then a tensile test was performed using EZ-test (manufactured by Shimadzu Corporation). The distance between the grips was 30 mm and the test speed was 10 mm / min.
３－２．成形性（成形可能温度）
　作製したフィルムから、５ｃｍ四方の正方形の評価用フィルムを切り出した。評価用フィルムを２５℃、６０％ＲＨの環境下で１時間放置した。次いで、国際公開第２０１８／０７４２６１号における発明を実施するための形態に記載されたラッピング錠の製造方法に準拠した、フィルムを加熱するためのヒーターを備えるラッピング製剤製造装置を用いて、内径７．５ｍｍの円柱状部分を有する型にフィルムを押し当て、フィルムと型との間の空隙を陰圧にすることにより、カップ部を形成した。フィルムを加熱するためヒーターの装置設定温度を変えながら成形試験を行い、形成されたカップ部を目視により観察した。型の円柱状部分の壁面を綺麗に反映した形状を有するカップ部が形成された場合を「成形可」と判定し、型の円柱状部分の内径よりも拡がった形状を有するカップ部が形成された場合を「成形不可」と判定した。図３は、成形試験により形成されたカップ部の例を示す写真である。図３のうち、「１」は「成形可」の例で、「２」及び「３」は「成形不可」の例である。「成形可」のカップ部が形成された装置設定温度のうち、最も低い温度を「成形可能設定温度」として記録した。例えば、フィルムを加熱するためのヒーターの設定温度が４００℃程度のとき、ヒーター出口の温度は３０５～３１０℃で、そのときのフィルム上面付近温度は２３０℃で、そのときのフィルム下面温度は最大で１２０℃であった。 3-2. Formability (moldable temperature)
A 5 cm square evaluation film was cut out from the produced film. The evaluation film was left at 25 ° C. and 60% RH for 1 hour. Next, an inner diameter 7. The cup portion was formed by pressing the film against a mold having a columnar portion of 5 mm and creating a negative pressure in the gap between the film and the mold. A molding test was performed while changing the device set temperature of the heater to heat the film, and the formed cup portion was visually observed. When a cup portion having a shape that beautifully reflects the wall surface of the columnar portion of the mold is formed, it is judged as "moldable", and a cup portion having a shape wider than the inner diameter of the cylindrical portion of the mold is formed. In this case, it was determined that molding was not possible. FIG. 3 is a photograph showing an example of a cup portion formed by a molding test. In FIG. 3, "1" is an example of "moldable", and "2" and "3" are examples of "non-moldable". Among the device set temperatures in which the "moldable" cup portion was formed, the lowest temperature was recorded as the "moldable set temperature". For example, when the set temperature of the heater for heating the film is about 400 ° C, the temperature of the heater outlet is 305 to 310 ° C, the temperature near the upper surface of the film at that time is 230 ° C, and the temperature of the lower surface of the film at that time is the maximum. It was 120 ° C.
４．結果
　評価結果が表１～４に示される。添加剤としてクエン酸トリエチル、トリアセチン、プロピレングリコール又はポリエチレングリコールを含む処方のフィルムは、添加剤未添加の処方０のフィルムと比較して低い成形温度で適切にカップ部を形成できることが確認された。処方６の場合、ヒーターの設定温度２４５℃で成形可であったものの、カップ部にしわの発生が認められた。 4. Results The evaluation results are shown in Tables 1 to 4. It was confirmed that the film of the formulation containing triethyl citrate, triacetin, propylene glycol or polyethylene glycol as an additive can appropriately form a cup portion at a lower molding temperature as compared with the film of formulation 0 without the additive. In the case of Formulation 6, although molding was possible at the set temperature of the heater of 245 ° C., wrinkles were observed in the cup portion.
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000002
Figure JPOXMLDOC01-appb-T000002
Figure JPOXMLDOC01-appb-T000003
Figure JPOXMLDOC01-appb-T000003
Figure JPOXMLDOC01-appb-T000004
Figure JPOXMLDOC01-appb-T000004
　１…カップ部用フィルム、１Ａ…底部、１Ｂ…壁部、１Ｃ…残部、２…蓋部用フィルム、２Ａ…天井部、２Ｂ…壁部、２Ｃ…残部、５…成形体、１０…カップ部、２０…蓋部、３０…型、５０…錠剤。 1 ... Cup film, 1A ... Bottom, 1B ... Wall, 1C ... Remaining, 2 ... Cover film, 2A ... Ceiling, 2B ... Wall, 2C ... Remaining, 5 ... Molded body, 10 ... Cup , 20 ... lid, 30 ... mold, 50 ... tablets.

Claims (12)

  1. 　ヒプロメロース又はヒドロキシプロピルセルロースのうち少なくとも一方のポリマーと、
    　クエン酸トリエチル、トリアセチン、プロピレングリコール、エチレングリコール、ポリエチレングリコール及び糖アルコールからなる群より選ばれる少なくとも１種の添加剤と、
    を含み、薬効成分を含む成形体をラッピングするために用いられるフィルム。     With at least one polymer of hypromellose or hydroxypropyl cellulose,
    At least one additive selected from the group consisting of triethyl citrate, triacetin, propylene glycol, ethylene glycol, polyethylene glycol and sugar alcohols, and
    A film used for wrapping a molded product containing a medicinal ingredient.
  2. 　前記添加剤の含有量が、前記ポリマー及び前記添加剤の合計量を基準として５～３０質量％である、請求項１に記載のフィルム。 The film according to claim 1, wherein the content of the additive is 5 to 30% by mass based on the total amount of the polymer and the additive.
  3. 　前記フィルムの引張弾性率が８００ＭＰａ以上である、請求項１又は２に記載のフィルム。 The film according to claim 1 or 2, wherein the film has a tensile elastic modulus of 800 MPa or more.
  4. 　前記フィルムが色素を更に含む、請求項１～３のいずれか一項に記載のフィルム。 The film according to any one of claims 1 to 3, wherein the film further contains a dye.
  5. 　前記添加剤がクエン酸トリエチル、トリアセチン、又はこれらの組み合わせである、請求項１～４のいずれか一項に記載のフィルム。 The film according to any one of claims 1 to 4, wherein the additive is triethyl citrate, triacetin, or a combination thereof.
  6. 　前記ポリマー及び前記添加剤を含む基材フィルムと、前記基材フィルム上に設けられた接着層とを有する、請求項１～５のいずれか一項に記載のフィルム。 The film according to any one of claims 1 to 5, which has a base film containing the polymer and the additive, and an adhesive layer provided on the base film.
  7. 　加熱された当該フィルムを型に押し当てることにより、薬効成分を含む成形体を挿入するためのカップ部を形成することを含む方法により錠剤を製造するために用いられる、請求項１～６のいずれか一項に記載のフィルム。 Any of claims 1 to 6, which is used for producing a tablet by a method including forming a cup portion for inserting a molded product containing a medicinal ingredient by pressing the heated film against a mold. The film described in item 1.
  8. 　当該フィルムのうち前記カップ部以外の残部を除去することを更に含む方法により錠剤を製造するために用いられる、請求項７に記載のフィルム。 The film according to claim 7, wherein the film is used for producing a tablet by a method further comprising removing a portion other than the cup portion of the film.
  9. 　加熱された請求項１～６のいずれか一項に記載のフィルムを型に押し当てることにより、開口を形成しているカップ部を形成することと、
    　前記カップ部内に、薬効成分を含む成形体を挿入することと、
    　前記開口を塞ぐ蓋部を蓋部用フィルムによって形成し、それにより前記蓋部及び前記カップ部によって前記成形体をラッピングすることと、
    を含む、錠剤を製造する方法。     By pressing the heated film according to any one of claims 1 to 6 against a mold, a cup portion forming an opening is formed.
    Inserting a molded product containing a medicinal ingredient into the cup portion
    The lid portion that closes the opening is formed by a film for a lid portion, whereby the molded body is wrapped by the lid portion and the cup portion.
    How to make tablets, including.
  10. 　前記カップ部内に前記成形体が挿入された後、前記フィルムのうち前記カップ部以外の残部を除去することを更に含む、請求項９に記載の方法。 The method according to claim 9, further comprising removing the rest of the film other than the cup portion after the molded body is inserted into the cup portion.
  11. 　薬効成分を含む成形体と、
    　前記成形体を収容し、開口を形成しているカップ部と、
    　前記開口を塞ぐ蓋部と、
    を備え、
    　前記成形体が前記蓋部及び前記カップ部によってラッピングされており、
    　前記カップ部が請求項１～６のいずれか一項に記載のフィルムである、
    錠剤。     Molds containing medicinal ingredients and
    A cup portion that houses the molded body and forms an opening, and
    The lid that closes the opening and
    Equipped with
    The molded product is wrapped by the lid portion and the cup portion.
    The film according to any one of claims 1 to 6, wherein the cup portion is the film according to any one of claims 1 to 6.
    tablet.
  12. 　薬効成分を含む成形体を、請求項１～６のいずれか一項に記載のフィルムを含む１枚以上のフィルムによってラッピングすることを含む、錠剤の形状保持性及び／又は化学的安定性を向上する方法。 Improving the shape retention and / or chemical stability of tablets, which comprises wrapping a molded product containing a medicinal ingredient with one or more films containing the film according to any one of claims 1 to 6. how to.
PCT/JP2021/021193 2020-06-04 2021-06-03 Film for wrapping tablets WO2021246487A1 (en)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2013203523A (en) * 2012-03-28 2013-10-07 Lintec Corp Web position adjustment method, web bonding method, manufacturing method of orally administered drug, and manufacturing device of orally administered drug
WO2018074261A1 (en) * 2016-10-17 2018-04-26 第一三共株式会社 Enclosing container manufacturing method and manufacturing device

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2013203523A (en) * 2012-03-28 2013-10-07 Lintec Corp Web position adjustment method, web bonding method, manufacturing method of orally administered drug, and manufacturing device of orally administered drug
WO2018074261A1 (en) * 2016-10-17 2018-04-26 第一三共株式会社 Enclosing container manufacturing method and manufacturing device

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